Regulation of gene transcription is the primary process by which a cell controls the appropriate expression of the multitude of genes necessary for growth and differentiation. The selective expression of genes at appropriate times is highly specialized in cells of multicellular organisms and permits the cells to perform "housekeeping" functions and respond to changes in their environment. These changes occur as a result of extracellular signals from a variety of sources such as hormones, neurotransmitters, and growth and differentiation factors.
Gene transcription is controlled by a regulator of gene transcription (RGT). RGTs act by binding to a short segment of DNA (transcription control element, TCE) located near the site of transcription initiation. Binding of an RGT to the target TCE activates transcription of the gene. RGTs contain a variety of structural motifs that, alone or in combination with one another, permit them to recognize and bind to the wide variety of TCEs. One group of RGTs have an amino acid motif known as a leucine zipper. A periodic repetition of leucine residues at every sixth to seventh position is characteristic of the leucine zipper motif, which is present in many gene regulatory proteins (Busch S. J. et al. (1990) Trends Genet. 6:36-40).
The leucine zipper-containing RGT, TSC-22, is rapidly and transiently induced in rodents by transforming growth factor beta (TGF; Shibanuma M. et al. (1992) J. Biol. Chem. 267:10219-10224). TGF functions in a variety of biological functions, particularly those involving cell growth and differentiation. The TSC-22 protein has been found in both the cell cytoplasm and nucleus, where it is thought to regulate gene expression. Several TSC-22 homologs have been identified and in many cases, its role in development has been confirmed. For example, the TSC-22 homolog, "shortsighted", is necessary for several developmental processes in Drosophila melanogaster, particularly photoreceptor differentiation. The shortsighted homolog interacts with several known development factors, including hedgehog, decapentaplegic, and wingless. Two human homologs of rodent TSC-22 have been described, hDIP (Vogel P. et al. (1996) Biochim. Biophys. Acta. 1309:200-204) and hTSC-22 (Jay P. et al. (1996) Biochem. Biophy. Res. Commun. 222:821-826).
Discovery of proteins related to mouse TSC-22 and the polynucleotides encoding them satisfies a need in the art by providing new compositions useful in diagnosis, prevention, and treatment of respiratory, developmental, and neurological disorders.